Several monoalkylating carcinogens induce strong, presumably covalent bonds between biological macromolecules. Complexes between DNA and proteins; DNA and proteins, DNA and DNA; and DNA and RNA; RNA and proteins; and RNA and RNA were recently observed in our laboratory. We intend to extend these observations by systematicaaly studying other carcinogenic chemicals and to assess the degree to which the formation of such intermolecular bridges may be involved in malignant transformation in vivo. Toward this end, the nucleic acids alone and in various combinations with other cellular macromolecules and isolated cell orgenelles will be exposed to chemical carcinogers and to tumor producing doses of radiation under a variety of experimental conditions (pH, varying concentrations of mono-and divalent cations, terperature etc). In separate experiments, purified chromatin will be the target for chemical carcinogens and radiation. The formation of intermolecular complexes will be monitored by several independent techniques. In the second part of this study, cells in culture and intact animals will be treated with carcinogens and radiation and correlations will be sought between the neoplastic transformation on one hand and the formation of such complexes on the other. We expect that these studies will increase our understanding of the mechanisms leading to malignant transformation in animal cells.